Bottom Line:
We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%).Natural isotope distributions play a major role inbroadening peaks associated with individual proteins.The model described here is capable of simulating realistic mass spectra.

Background: Mass spectrometry is actively being used to discover disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological fluids. The potential importance of these clinical applications has made the development of better methods for processing and analyzing the data an active area of research. It is, however, difficult to determine which methods are better without knowing the true biochemical composition of the samples used in the experiments.

Methods: We developed a mathematical model based on the physics of a simple MALDI-TOF mass spectrometer with time-lag focusing. Using this model, we implemented a statistical simulation of mass spectra. We used the simulation to explore some of the basicoperating characteristics of MALDI or SELDI instruments.

Results: The simulation reproduced several characteristics of actual instruments. We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%). The accuracy of calibration based on external standards decays rapidly outside the range spanned by the calibrants. Natural isotope distributions play a major role inbroadening peaks associated with individual proteins. The area of a peak is a more accurate measure of its size than the height.

Conclusions: The model described here is capable of simulating realistic mass spectra. The simulation should become a useful tool forgenerating spectra where the true inputs are known, allowing researchers to evaluate the performance of new methods for processing and analyzing mass spectra.

f1-cin-01-41: (Top) Simplified schematic of a MALDI-TOF instrument with time-lag focusing. Samples are inserted on a metal plate into a vacuum chamber where they are ionized by a laser. Electric fields between the sample plate and two charged grids accelerate the ions into a drift tube, where they continue until they strike a detector. (Bottom) Voltage potentials along the instrument. The sample plate and grid start at the same potential, but the potential is raised after a brief delay.

Mentions:
We developed code to simulate experiments based on a physical model of a linear MALDI-TOF instrument with time-lag focusing or delayed extraction (Wiley and McLaren, 1955; Vestal et al., 1995). Such an instrument is illustrated schematically in Figure 1. The flight path of a particle in this instrument passes through three regions:

f1-cin-01-41: (Top) Simplified schematic of a MALDI-TOF instrument with time-lag focusing. Samples are inserted on a metal plate into a vacuum chamber where they are ionized by a laser. Electric fields between the sample plate and two charged grids accelerate the ions into a drift tube, where they continue until they strike a detector. (Bottom) Voltage potentials along the instrument. The sample plate and grid start at the same potential, but the potential is raised after a brief delay.

Mentions:
We developed code to simulate experiments based on a physical model of a linear MALDI-TOF instrument with time-lag focusing or delayed extraction (Wiley and McLaren, 1955; Vestal et al., 1995). Such an instrument is illustrated schematically in Figure 1. The flight path of a particle in this instrument passes through three regions:

Bottom Line:
We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%).Natural isotope distributions play a major role inbroadening peaks associated with individual proteins.The model described here is capable of simulating realistic mass spectra.

Background: Mass spectrometry is actively being used to discover disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological fluids. The potential importance of these clinical applications has made the development of better methods for processing and analyzing the data an active area of research. It is, however, difficult to determine which methods are better without knowing the true biochemical composition of the samples used in the experiments.

Methods: We developed a mathematical model based on the physics of a simple MALDI-TOF mass spectrometer with time-lag focusing. Using this model, we implemented a statistical simulation of mass spectra. We used the simulation to explore some of the basicoperating characteristics of MALDI or SELDI instruments.

Results: The simulation reproduced several characteristics of actual instruments. We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%). The accuracy of calibration based on external standards decays rapidly outside the range spanned by the calibrants. Natural isotope distributions play a major role inbroadening peaks associated with individual proteins. The area of a peak is a more accurate measure of its size than the height.

Conclusions: The model described here is capable of simulating realistic mass spectra. The simulation should become a useful tool forgenerating spectra where the true inputs are known, allowing researchers to evaluate the performance of new methods for processing and analyzing mass spectra.